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Cited by 366

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

β-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice

Open access
Morris, John P., Cano, David A., Sekine, Shigeki, Wang, Sam C., Hebrok, Matthias·2010·Journal of Clinical Investigation

Abstract

Cellular plasticity in adult organs is involved in both regeneration and carcinogenesis. WT mouse acinar cells rapidly regenerate following injury that mimics acute pancreatitis, a process characterized by transient reactivation of pathways involved in embryonic pancreatic development. In contrast, such injury promotes the development of pancreatic ductal adenocarcinoma (PDA) precursor lesions in mice expressing a constitutively active form of the GTPase, Kras, in the exocrine pancreas. The molecular environment that mediates acinar regeneration versus the development of PDA precursor lesions is poorly understood. Here, we used genetically engineered mice to demonstrate that mutant Kras promotes acinar-to-ductal metaplasia (ADM) and pancreatic cancer precursor lesion formation by blocking acinar regeneration following acute pancreatitis. Our results indicate that beta-catenin is required for efficient acinar regeneration. In addition, canonical beta-catenin signaling, a pathway known to regulate embryonic acinar development, is activated following acute pancreatitis. This regeneration-associated activation of beta-catenin signaling was not observed during the initiation of Kras-induced acinar-to-ductal reprogramming. Furthermore, stabilized beta-catenin signaling antagonized the ability of Kras to reprogram acini into PDA preneoplastic precursors. Therefore, these results suggest that beta-catenin signaling is a critical determinant of acinar plasticity and that it is inhibited during Kras-induced fate decisions that specify PDA precursors, highlighting the importance of temporal regulation of embryonic signaling pathways in the development of neoplastic cell fates.

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Metadata

Authors
Morris, J. P., Cano, D. A., Sekine, S., Wang, S. C., & Hebrok, M.
Venue
Journal of Clinical Investigation
Published
2010-02-01
Volume
120
Issue
2
Pages
508-520
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1987220381
Cited by
366
References
48
FWCI
11.97
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: β-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. https://app.cochat.ai/papers/10.1172/jci40045
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Morris, J. P., Cano, D. A., Sekine, S., Wang, S. C., & Hebrok, M. (2010). β-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci40045

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.